Bromocriptine Attenuated Ulcerative Colitis and Colonic Inflammation by Inhibiting IL-1β, Likely through NF-κB Down-regulation: Integrated Network Pharmacology and in vivo Experimental Validation

INTRODUCTION: Gastrointestinal dopamine (DA) plays a crucial role in maintaining gut homeostasis. In patients with ulcerative colitis (UC), a decrease in DA levels due to changes in the gut microbiome can activate immune cells in the colon's mucosal layer, leading to the secretion of various inflammatory mediators and ultimately causing damage to the colonic mucosa. In the present study, we initially analysed integrated network pharmacology and investigated the protective effect of bromocriptine (BRO), a dopamine D2 receptor (D2R) agonist, on acetic acid (AA)-induced UC in rats. METHODS: Wistar rats were randomly divided into six groups (N=6/group). The intrarectal administration of AA induced UC. Treatment groups (III-IV) received three doses (2, 5, and 10 mg/kg) of BRO once daily for seven days. Group VI animals were administered mesalamine. On the eighth day, the animals were sacrificed to evaluate the lesion scores, ulcer indices, histopathological findings, nitric oxide (NO) levels, and myeloperoxidase (MPO). Finally, tissue levels of interleukin (IL-1β) and nuclear factor kappa B (NF-κB) were measured using ELISA. RESULTS: BRO treatment effectively improved the disease severity index (DAI), colonic lesion score, and ulcer index in rats with AA-induced UC. Histopathological studies revealed that treatment with BRO limited mucosal damage and neutrophil extravasation in colonic tissue. Moreover, biochemical assessments of MPO and NO showed a significant decrease in the levels of both inflammatory mediators following treatment with BRO. Additionally, the results indicated a reduction in the expression of IL-1β and NF-κB in colonic tissue, further supporting the amelioration of colonic inflammation caused by BRO. DISCUSSION: The present research demonstrated that BRO exerts a protective effect by influencing the expression of IL-1β and NF-κB in rats with AA-induced UC, thus restricting the activity of immune cells in the colonic mucosa. CONCLUSION: Findings of this research suggest that BRO may be a promising therapeutic agent for the management of UC.